The ACUFLASH study. Acupuncture treatment for postmenopausal hot flashes : can traditional Chinese acupuncture in addition to self-care reduce hot flash frequency and intensity, compared with self-care alone?

Papers 1, 2 and 3 of the thesis are not available in Munin due to publishers' restrictions: 1. Borud EK, Alraek T, White A, Fonnebo V, Eggen AE, Hammar M, Astrand LL, Theodorsson E, Grimsgaard S: «The Acupuncture on Hot Flushes Among Menopausal Women (ACUFLASH) study, a randomized controlled trial», Menopause 2009, 16(3):484-493 (Lippincott). Available at http://dx.doi.org/10.1097/gme.0b013e31818c02ad 2. Borud EK, Alraek T, White A, Grimsgaard S: «The acupuncture treatment for postmenopausal hot flushes (Acuflash) study: traditional Chinese medicine diagnoses and acupuncture points used, and their relation to the treatment response», Acupuncture in Medicine 2009, 27;101-108 (British Medical Acupuncture Society). Available at http://dx.doi.org/10.1136/aim.2009.000612 3. Borud EK, Martinussen M, Eggen AE, Grimsgaard S: «The Women's Health Questionnaire (WHQ): a psychometric evaluation of the 36-item Norwegian version», Scandinavian journal of psychology 2009, 50: 183-189 (Wiley-Blackwell). Available at http://dx.doi.org/10.1111/j.1467-9450.2008.00701.xIntroduction. Hot flashes and night sweats are the most prevalent symptoms in menopause. Hormone therapy with oestrogen is considered the most effective treatment. However, recent research show that long term use of oestrogen increases the risk of serious adverse effects, and women and their health care providers are looking for alternatives. Acupuncture is one of the most frequently used complementary therapies in Norway, and is considered safe in the hands of competent practitioners. Previous data on acupuncture treatment for hot flashes were insufficient to draw any conclusions on the effect, but sufficient to justify further research. Acupuncture affects beta-endorphin activity in the central nervous system, and may thus also affect the calcitonin gene-related peptide (CGRP) excretion. CGRP is a potent vasodilator and stimulator of cholinergic sweat glands, and has been suggested as a mediator of hot flashes and sweating in postmenopausal women. The Women‟s Health Questionnaire (WHQ) is a health-related quality of life questionnaire, designed specifically to study possible changes that occur during menopause. Aims. We wanted to estimate the effectiveness of acupuncture in practice. Thus, our objective was to assess the effectiveness of a policy of use of traditional Chinese medicine (TCM) acupuncture plus self-care on hot flash frequency in postmenopausal women, compared with a policy of use of self-care alone. The effects on hot flash intensity (0-10 scale) and sleep and on health-related quality of life as measured by the Women‟s Health Questionnaire (WHQ) were also assessed, as were the changes in urine excretion of CGRP. Secondary research questions were: “do TCM diagnoses predict the overall treatment response”, and “are patients with different TCM diagnoses likely to experience a differential response in their symptoms”? The Norwegian version of the WHQ had not been validated, and the participants in the Acuflash study reported more vasomotor symptoms than participants in prior studies of the WHQ. Therefore, it was necessary to evaluate the psychometric properties of the instrument. Materials and methods. The study was a multicenter, pragmatic, randomized, controlled trial with two parallel arms. Participants were postmenopausal women experiencing on average seven or more hot flashes per 24 hours during seven consecutive days. The acupuncture group received ten individualized TCM acupuncture treatment sessions after initial TCM diagnosis, the control group received advice on self-care only. Frequency and severity (0-10 scale) of hot flashes and hours of sleep per night were registered in a diary. Urine excretion of calcitonin gene-related peptide (CGRP) was assessed at baseline and after 12 weeks. Primary endpoint was change in mean hot flash frequency from baseline to 12 weeks. Secondary endpoint was change in health related quality of life measured by the Women‟s Health Questionnaire (WHQ). Primary and secondary endpoints were also assessed at six and 12 months after study start. The acupuncturists recorded TCM diagnoses and acupuncture points for each treatment session. Treatment reactions and adverse events were also recorded. The evaluation of the WHQ was performed by examining the factor structure of the Norwegian version, assessing the internal consistency reliability and floor- and ceiling effects, and by exploring the construct validity of the instrument by comparing the WHQ to instruments measuring related constructs. Results. Hot flash frequency decreased by 5.8 per 24 hours in the acupuncture group (n = 134) and 3.7 per 24 hours in the control group (n=133), a difference of 2.1, p < 0.001. Hot flash intensity decreased by 3.2 units in the acupuncture group and 1.8 units in the control group, a difference of 1.4, p < 0.001. The acupuncture group experienced statistically significant improvements in the vasomotor, sleep and somatic symptoms dimensions of the Women‟s Health Questionnaire, compared with the control group. Urine CGRP excretion remained unchanged from baseline to week 12. We did not find statistically significant differences between the study groups regarding primary and secondary endpoint at six and 12 months after study start. Fifty percent of the participants in the acupuncture group were diagnosed with Kidney Yin Xu as their primary TCM syndrome diagnosis. No statistically significant differences were demonstrated between the syndrome groups regarding the distribution of responders and non-responders, nor regarding the changes in health-related quality of life scores. A core of common acupuncture points (SP6, HT6, KI7, KI6, CV4, LU7, LI4, and LR3) were used in all the syndromes and in addition multiple idiosyncratic points. Core point selection and frequency of use did not differ between responders and nonresponders. No serious adverse events were reported. Some deficiencies in the WHQ questionnaire were observed when applied to the present sample, including an unclear factor structure, low alpha values for some dimensions, and a strong floor effect in the vasomotor symptoms dimension. Conclusions. Use of TCM acupuncture in addition to self care can contribute to a quicker reduction of hot flash frequency and increase in health related quality of life among postmenopausal women, but probably has no long term effects. Other factors than the TCM syndrome diagnoses and the point selection may be of importance regarding the outcome of the treatment. When evaluating the psychometric properties of the WHQ, the total scale score appeared reliable. However, care should be taken when interpreting some of the subscales when the instrument is applied on women with a high frequency of hot flashes.Kan tradisjonell kinesisk akupunktur i tillegg til egenomsorg redusere frekvens og intensitet av hetetokter i overgangsalderen, sammenlignet med kun egenomsorg? Hetetokter og nattsvette er de vanligste symptomene forbundet med overgangsalderen hos kvinner, og mange er mye plaget. Hormonbehandling med østrogen er den mest effektive behandlingen for disse plagene, men nyere studier har vist at hormonterapi kan være forbundet med alvorlige bivirkninger. Mange kvinner og leger ser etter alternativer. Akupunktur er en av de mest brukte alternative behandlingsformene i Norge. Tidligere forskning på effekten av akupunktur på hetetokter i overgangsalderen var ikke tilstrekkelig til å dra noen konklusjoner, men interessant nok til å rettferdiggjøre videre forskning. Vi ønsket å evaluere effekten av akupunkturbehandling og egenomsorg, sammenliknet med kun egenomsorg, på frekvens og intensitet av hetetokter og på helserelatert livskvalitet hos kvinner i overgangsalderen. ACUFLASH - studien var en pragmatisk, multisenter, randomisert, kontrollert studie med to grupper deltakere. Deltakerne var kvinner i overgangsalderen med i gjennomsnitt minst syv hetetokter i døgnet over en periode på syv påfølgende dager. Kvinnene i akupunkturgruppa (n=134) fikk 10 akupunkturbehandlinger i løpet av 10 uker i tillegg til egenomsorg, og kvinnene i kontrollgruppa (n=133) fikk kun egenomsorg. Frekvensen og intensiteten (0-10 skala) av hetetokter ble registrert i en dagbok. Helserelatert livskvalitet ble målt med spørreskjemaet ”Spørreskjema om helse for kvinner” (Women’s Health Questionnaire – WHQ). Etter 12 uker var hetetoktfrekvensen redusert med 5,8 hetetokter pr. døgn i akupunkturgruppa og 3,7 hetetokter pr. døgn i kontrollgruppa, en statistisk signifikant forskjell på 2,1 hetetokter pr. døgn. Reduksjonen i intensitet og økningen i livskvalitet var også signifikant større i akupunkturgruppa etter 12 uker. Seks og 12 måneder etter studiestart var det ingen forskjell mellom gruppene vedrørende hetetokter eller livskvalitet. Vi konkluderte med at akupunkturbehandling i tillegg til egenbehandling kan bidra til en raskere reduksjon av hetetokter og bedring av helserelatert livskvalitet hos kvinner i overgangsalderen, men at behandlingen sannsynligvis ikke har noen langtidseffekt

Social and life skills in adolescents who have self-harmed: analysis of survey responses from a national sample of adolescents in Norway

publishedVersio

The ACUFLASH study. Acupuncture treatment for postmenopausal hot flashes : can traditional Chinese acupuncture in addition to self-care reduce hot flash frequency and intensity, compared with self-care alone?

Introduction. Hot flashes and night sweats are the most prevalent symptoms in menopause. Hormone therapy with oestrogen is considered the most effective treatment. However, recent research show that long term use of oestrogen increases the risk of serious adverse effects, and women and their health care providers are looking for alternatives. Acupuncture is one of the most frequently used complementary therapies in Norway, and is considered safe in the hands of competent practitioners. Previous data on acupuncture treatment for hot flashes were insufficient to draw any conclusions on the effect, but sufficient to justify further research. Acupuncture affects beta-endorphin activity in the central nervous system, and may thus also affect the calcitonin gene-related peptide (CGRP) excretion. CGRP is a potent vasodilator and stimulator of cholinergic sweat glands, and has been suggested as a mediator of hot flashes and sweating in postmenopausal women. The Women‟s Health Questionnaire (WHQ) is a health-related quality of life questionnaire, designed specifically to study possible changes that occur during menopause. Aims. We wanted to estimate the effectiveness of acupuncture in practice. Thus, our objective was to assess the effectiveness of a policy of use of traditional Chinese medicine (TCM) acupuncture plus self-care on hot flash frequency in postmenopausal women, compared with a policy of use of self-care alone. The effects on hot flash intensity (0-10 scale) and sleep and on health-related quality of life as measured by the Women‟s Health Questionnaire (WHQ) were also assessed, as were the changes in urine excretion of CGRP. Secondary research questions were: “do TCM diagnoses predict the overall treatment response”, and “are patients with different TCM diagnoses likely to experience a differential response in their symptoms”? The Norwegian version of the WHQ had not been validated, and the participants in the Acuflash study reported more vasomotor symptoms than participants in prior studies of the WHQ. Therefore, it was necessary to evaluate the psychometric properties of the instrument. Materials and methods. The study was a multicenter, pragmatic, randomized, controlled trial with two parallel arms. Participants were postmenopausal women experiencing on average seven or more hot flashes per 24 hours during seven consecutive days. The acupuncture group received ten individualized TCM acupuncture treatment sessions after initial TCM diagnosis, the control group received advice on self-care only. Frequency and severity (0-10 scale) of hot flashes and hours of sleep per night were registered in a diary. Urine excretion of calcitonin gene-related peptide (CGRP) was assessed at baseline and after 12 weeks. Primary endpoint was change in mean hot flash frequency from baseline to 12 weeks. Secondary endpoint was change in health related quality of life measured by the Women‟s Health Questionnaire (WHQ). Primary and secondary endpoints were also assessed at six and 12 months after study start. The acupuncturists recorded TCM diagnoses and acupuncture points for each treatment session. Treatment reactions and adverse events were also recorded. The evaluation of the WHQ was performed by examining the factor structure of the Norwegian version, assessing the internal consistency reliability and floor- and ceiling effects, and by exploring the construct validity of the instrument by comparing the WHQ to instruments measuring related constructs. Results. Hot flash frequency decreased by 5.8 per 24 hours in the acupuncture group (n = 134) and 3.7 per 24 hours in the control group (n=133), a difference of 2.1, p < 0.001. Hot flash intensity decreased by 3.2 units in the acupuncture group and 1.8 units in the control group, a difference of 1.4, p < 0.001. The acupuncture group experienced statistically significant improvements in the vasomotor, sleep and somatic symptoms dimensions of the Women‟s Health Questionnaire, compared with the control group. Urine CGRP excretion remained unchanged from baseline to week 12. We did not find statistically significant differences between the study groups regarding primary and secondary endpoint at six and 12 months after study start. Fifty percent of the participants in the acupuncture group were diagnosed with Kidney Yin Xu as their primary TCM syndrome diagnosis. No statistically significant differences were demonstrated between the syndrome groups regarding the distribution of responders and non-responders, nor regarding the changes in health-related quality of life scores. A core of common acupuncture points (SP6, HT6, KI7, KI6, CV4, LU7, LI4, and LR3) were used in all the syndromes and in addition multiple idiosyncratic points. Core point selection and frequency of use did not differ between responders and nonresponders. No serious adverse events were reported. Some deficiencies in the WHQ questionnaire were observed when applied to the present sample, including an unclear factor structure, low alpha values for some dimensions, and a strong floor effect in the vasomotor symptoms dimension. Conclusions. Use of TCM acupuncture in addition to self care can contribute to a quicker reduction of hot flash frequency and increase in health related quality of life among postmenopausal women, but probably has no long term effects. Other factors than the TCM syndrome diagnoses and the point selection may be of importance regarding the outcome of the treatment. When evaluating the psychometric properties of the WHQ, the total scale score appeared reliable. However, care should be taken when interpreting some of the subscales when the instrument is applied on women with a high frequency of hot flashes

The acupuncture on hot flashes among menopausal women (ACUFLASH) study : observational follow up results at six and 12 months

Objective: The previously published ACUFLASH study compared the effectiveness of individualized acupuncture treatment plus self-care versus self-care alone on hot flashes and health-related quality of life in postmenopausal women. This paper reports on the observational follow-up results at six and 12 months. Methods: The ACUFLASH study was a pragmatic, multicenter, randomized, controlled trial with two parallel arms, conducted in 2006-2007. The 267 participants were postmenopausal women experiencing, on average, 12.6 hot flashes per 24 hours. The acupuncture group received 10 individualized acupuncture treatments during 12 weeks and advice on self-care, and the control group received advice on self-care only. Hot flash frequency and intensity (0-10 scale) and hours of sleep per night were registered in a diary. Health-related quality of life was assessed by the Women‟s Health Questionnaire. Results: From baseline to six months, the mean reduction in hot flash frequency per 24 hours was 5.3 in the acupuncture group and 5.0 in the control group, a non-significant difference of 0.3. At 12 months, the mean reduction in frequency was 6.0 in the acupuncture group and 5.8 in the control group, a non-significant difference of 0.2. Differences in quality of life scores were not statistically significant at six and 12 months. Conclusion: The statistically significant differences between the study groups found at Week 12 were no longer present at six and 12 months. Acupuncture can contribute to a more rapid reduction of vasomotor symptoms and increase in health-related quality of life in postmenopausal women, but probably has no long-term effects

Disease-related mortality among 21,609 Norwegian male military peacekeepers deployed to Lebanon between 1978 and 1998

Objective: To investigate external-cause mortality among 21 609 Norwegian male military peacekeepers deployed to Lebanon during 1978–1998. Methods: The cohort was followed from first day of deployment through 2013, and mortality during deployment and post discharge was assessed using standardized mortality ratios (SMR) calculated from national rates in Norway. Poisson regression was used to see the effect of high- versus low-conflict exposure. Results: For the total cohort, external-cause mortality was within expected values during deployment (SMR=0.80) and post discharge (SMR=1.05). In the low-conflict exposure group, a lower mortality from all external causes (SMR=0.77), transport accidents (SMR=0.55), and accidental poisoning (SMR=0.53) was seen. The high-conflict exposure group showed an elevated mortality from all external causes (SMR=1.20), transport accidents (SMR=1.51), and suicide (SMR=1.30), but these risks were elevated only during the first 5 years after discharge. This group also showed elevated mortality from all external causes (RR=1.49), and for transport accidents (RR=3.30) when compared with the low-conflict exposure group. Conclusions: Overall external-cause mortality among our peacekeepers was equal to national rates during deployment and post discharge. High conflict exposure was associated with elevated mortality from all external causes, transport accidents, and suicide during the first 5 years after discharge from service

Pooled analysis of all-cause and cause-specific mortality among Nordic military veterans following international deployment

Objectives - To investigate all-cause and cause-specific mortality risks, including deaths from external, cardiovascular and cancer causes, among deployed Nordic military veterans in comparison to the general population in each country. Design - Pooled analysis. Setting - Denmark, Norway, Finland and Sweden. Participants - Military veterans deployed between 1990 and 2010 were followed via nationwide registers and compared with age-sex-calendar-year-specific rates in the general population using pooled standardised mortality ratios (SMRs). Main outcomes - All-cause and cause-specific mortality retrieved from each country’s Causes of Death Register, including deaths from external, cardiovascular and cancer causes. Results - Among 83 584 veterans 1152 deaths occurred of which 343 were from external causes (including 203 suicides and 129 traffic/transport accidents), 134 from cardiovascular causes and 297 from neoplasms. Veterans had a lower risk of death from any cause (pooled SMR 0.58, 95% CI 0.52 to 0.64), external causes (0.71, 95% CI 0.64 to 0.79), suicide (0.77, 95% CI 0.67 to 0.89), cardiovascular causes (0.54, 95% CI 0.46 to 0.64) and neoplasms (0.78, 95% CI 0.70 to 0.88). There was no difference regarding traffic/transport accidents for the whole period (1.10, 95% CI 0.92 to 1.31) but the pooled point estimate was elevated, though not statistically significant, during the first 5 years (1.17, 95% CI 0.89 to 1.53) but not thereafter (1.01, 95% CI 0.77 to 1.34). For all other causes of death, except suicide, statistically significantly lower risk among veterans was observed both during the first 5 years and thereafter. For suicide, no difference was observed beyond 5 years. Judged from the country-specific SMR estimates, there was a high degree of consistency although statistically significant heterogeneity was found for all-cause mortality. Conclusions - Nordic military veterans had lower overall and cause-specific mortality than the general population for most outcomes, as expected given the predeployment selection process. Though uncommon, fatal traffic/transport accidents were an exception with no difference between deployed military veterans and the general population

Predictors of gaming behavior among military peacekeepers - exploring the role of boredom and loneliness in relation to gaming problems

The aim of the current study was to explore gaming problems in post-deployment veterans and to investigate whether boredom and loneliness can predict levels of gaming problems. The general well-being of veterans post their deployments to war zones is linked to an array of negative health consequences, and veterans may be at risk for developing gaming problems after homecomings. Problems that may be related to engagement in gaming include coping with negative emotions, such as boredom and loneliness, which are often faced by homecoming veterans as well. The sample in this study comprised Afghanistan veterans (N = 246), with a mean age of 37.5 years (standard deviation = 9.6 years), and 8.8% of the veterans showed symptoms indicative of problem gaming. This is not higher than that found in the general adult population in Norway. Logistic regression analyses showed that boredom proneness (lack of internal stimulation) and enhancement motivation were independent significant predictors of gaming problems, after controlling for age, gender, coping motivation, social motivation, anxiety, depression, loneliness, lack of external stimulation, hazardous drinking, and combat exposure. These factors accounted for as much as 65.8% of the variance in gaming problem status. We conclude that veterans who are highly motivated by enhancement motives and score low on lack of internal stimulation may be prone to developing gaming problems

Predictors of gaming behavior among military peacekeepers – exploring the role of boredom and loneliness in relation to gaming problems

The aim of the current study was to explore gaming problems in post-deployment veterans and to investigate whether boredom and loneliness can predict levels of gaming problems. The general well-being of veterans post their deployments to war zones is linked to an array of negative health consequences, and veterans may be at risk for developing gaming problems after homecomings. Problems that may be related to engagement in gaming include coping with negative emotions, such as boredom and loneliness, which are often faced by homecoming veterans as well. The sample in this study comprised Afghanistan veterans (N = 246), with a mean age of 37.5 years (standard deviation = 9.6 years), and 8.8% of the veterans showed symptoms indicative of problem gaming. This is not higher than that found in the general adult population in Norway. Logistic regression analyses showed that boredom proneness (lack of internal stimulation) and enhancement motivation were independent significant predictors of gaming problems, after controlling for age, gender, coping motivation, social motivation, anxiety, depression, loneliness, lack of external stimulation, hazardous drinking, and combat exposure. These factors accounted for as much as 65.8% of the variance in gaming problem status. We conclude that veterans who are highly motivated by enhancement motives and score low on lack of internal stimulation may be prone to developing gaming problems

Botulinum Toxin A in the treatment of frostbite sequelae–results from a blinded, early-phase, comparative trial

Introduction: Freezing Cold Injuries (FCI) have been associated with long-term sequelae including vasospasm. The aims of the pilot study are to explore the research methodology and investigate the tolerability and safety of treatment with Botulinum Toxin-A (BTX-A) in FCI Sequelae. Methodology: This pilot study tests the logistics, the treatment setting and the follow-up procedure in an early-phase, double-blinded, randomized, controlled trial study-design. The variables in the study were subjective symptoms, peripheral micro-vascularization/rewarming, somatosensory responsiveness, and generic measure of health status. Results: No major challenges or difficulties were noticed according to the protocol or the study methodology. The monitoring of tolerability and safety of treatment with BTX-A did not reveal any major unwanted and/or adverse reactions among the patients in the pilot study and no challenges occurred during data collection of endpoints. The study revealed an inaccuracy of the 2nd degree FCI diagnosis and uncover a need for relevant and sufficient clinical information for FCI classification. Conclusions: This pilot study showed the study methodology with minor adjustments is feasible in a future full-scale clinical trial. The recruitment process needs to be more refined to ensure that the eligible study participants are a homogenous group of FCI patients